High-Yield Total Synthesis of (−)-Strictinin through Intramolecular Coupling of Gallates

Abstract

This paper describes a total synthesis of (-)-strictinin, an ellagitannin that is 1-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl (HHDP)-β-D-glucose. In the study, total efficiency of the synthesis was improved to produce a 78% overall yield in 13 steps from D-glucose. In the synthesis, formation of the 4,6-(S)-HHDP bridge including the 11-membered bislactone ring was a key step, in which intramolecular aryl-aryl coupling was adopted. The coupling was oxidatively induced by CuCl2-n-BuNH2 with perfect control of the axial chirality, and the reaction conditions of this coupling were optimized thoroughly to achieve the quantitative formation of the bridge.

Total Synthesis of Ellagitannins <i>via</i> Sequential Site-Selective Functionalization of Unprotected D-Glucose

“…The intramolecular oxidative phenol coupling of the resulting phenol derivative was accomplished stereoselectively according to the excellent method developed by Yamada and colleagues. 25) In the presence of CuCl 2 /n-BuNH 2 , the oxidative phenol coupling between the 2-and the 3-gallates proceeded to give hexahydroxydiphenoyl (HHDP) derivative 16 with the complete stereo-control of the newly formed chiral axis (S) in (9 steps without including the steps for the construction of the HHDP moiety). In this synthesis, five galloyl(oxy) groups were sequentially introduced in the order C(1) (blue in Chart 2), C(4)-OH (brown in Chart 2), C(6)-OH (green in Chart 2) followed by C(2)-and C(3)-OH (yellow in Chart 2) into the unprotected D-glucose.…”

Total Syntheses of Laevigatins A and E

“…[14] Thus, diesterification of diol 12 with carboxylic acid 13 [20] using EDCI {1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide} and DMAP [4-(dimethylamino)pyridine] gave the corresponding bisgallate. [14] Thus, diesterification of diol 12 with carboxylic acid 13 [20] using EDCI {1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide} and DMAP [4-(dimethylamino)pyridine] gave the corresponding bisgallate.…”

“…Although a wide variety of biological activities have been reported for the ellagitannins, [1,2,9] the elucidation of their structure-activity relationships has been a problem due to the difficulty of obtaining a complete collection of systematically related analogues from nature. Fortunately, the synthesis of monomeric ellagitannins and their artificial analogues has progressed significantly, and much knowledge has been accumulated, [11][12][13][14][15][16][17][18][19][20][21][22][23][24] although the amounts of the compounds synthesized have been small in many cases. A considerable number of characterized compounds, which could be isolated only in trace amounts, have been left unexplored.…”

Application of the uridine auxotrophic host and synthetic nucleosides for a rapid selection of hydrolases from metagenomic libraries

“…2′,3′,5′‐ O ‐acetyluridine and 2′,3′,5′‐hexanoyluridine were prepared by adapting and modifying methods reported in the literature(García et al ., ; Michihata et al ., ; Gaubert et al ., ).…”